Sensory impairment, whether acute, transient, and/or chronic (e.g., pain, soreness, tingling, burning, numbness, altered proprioception, stiffness, sharp, etc.) in a patient's extremities can be associated with a number of conditions and result from a number of causes including both mechanical, biological, and chemical insult(s). One very common condition is peripheral neuropathy (e.g., diabetic neuropathy, neuropathy associated with chemotherapy, etc.). Peripheral neuropathy may occur when the nerves connecting an individual's spinal cord and brain to other parts of the body (peripheral nerves) become damaged and/or nerve transmission is interrupted. Damage/disruption to the peripheral nerves may cause symptoms such as, for example, tingling and numbness, lack of sensation, pain, balance and coordination impairment, diminished hot and cold sensation, hypersensitivity to hot and cold, phantom hot and cold sensations, muscle weakness, etc. that may most commonly begin in the hands or feet and may spread throughout the extremities, or that may, e.g., begin in the torso and spread throughout the torso and/or abdomen.
The nerve damage of peripheral neuropathy most commonly appears as a complication of another disorder such as diabetes or AIDS, or as a reaction to drugs, alcohol, or various chemicals (including some therapeutics such as chemotherapeutics). A large portion of peripheral neuropathy presentations, e.g., roughly 30%, are considered idiopathic, or of unknown origin, and can exist seemingly without causal pathology. Nerve damage can also result from viral and bacterial infections, rheumatoid arthritis, lupus, autoimmune disorders, exposure to toxins, cancer and/or cancer treatments, vitamin deficiencies, kidney disease, liver disease, or inherited/hereditary conditions. Other causes of peripheral neuropathy include trauma, penetrating or crush injuries, bruises, fractures, and dislocated bones. Nerve damage can also be present in situations lacking clear causal pathology that is diagnosed secondary to one or more other diseases. Nerve damage can also result from extended exposure to cold or heat, radiation and/or chemical therapy for cancer, excessive vomiting (which may occur during early pregnancy), and various other causes.
Exposure to toxic chemicals can cause neuropathy. Toxic chemicals that can cause neuropathy may include industrial agents such as, e.g., solvents, heavy metals such as lead, arsenic, mercury, pesticides, nitrous oxide, etc. Sniffing glue or other toxic compounds can also cause peripheral neuropathy. Likewise, nutritional deficiencies may cause peripheral neuropathy. Alcoholism may also be a cause of neuropathy. Further, roughly 33% of the total cases of peripheral neuropathy in the United States are related to diabetes while approximately 30% are idiopathic.
When a peripheral nerve is damaged, communication between the central nervous system and the area of the body served by the peripheral nerve is disrupted. The type of damage to the nerves influences the types of symptoms that may occur. For example, if the sensory nerve fibers are damaged, the patient will likely experience changes in sensation such as numbness or pain, either at the site of nerve damage, distant thereto, or both. In addition, pain perception may vary from one patient to another. For example, one may experience broad regions of numbness, others an aching sensation, and still others areas of both sharp and/or penetrating discomfort with surrounding areas of sensory disruption. These and other symptoms may occur alone and/or in various combinations that vary with time of day, season, activity, and variable external factors including, e.g., heat, cold, humidity, and/or barometric pressure. However, if the motor fibers are damaged, muscles may be affected, e.g., causing changes in the ability to move and/or balance properly. Reductions in the ability to move can diminish the range of motion in the affected areas. For example, the reductions in the ability to move, or alternations in motor function, can change gait and stance, and may contribute to, or be contributing factors for, lower back pain. Further, for example, intrinsic foot muscles can become weakened thereby predisposing one to mechanical foot pain or plantar fasciitis as the foot pronates upon weight bearing, which can also lead to mechanical and/or structural issues. These reductions in range of motion can also lead to what is called soft tissue contracture. This “shrinking” of the connective tissues, such as tendons and joint capsules, can further limit mobility. These soft tissue contractures by themselves can become painful and lead to a burning sensation called facial pain. Motor function problems can also lead to problems with balance and coordination. Thus, peripheral neuropathy can become a safety issue, for example, when a person can no longer feel how hard they are pushing on the gas or brake pedal, or even on which pedal their foot rests.
Patient afflicted with peripheral neuropathy may experience burning and/or freezing sensations, shooting pain (e.g., which may be worse at night), gradual muscular weakening, skin that is extremely sensitive to touch, and loss of balance or coordination. In extreme cases, such patients may lose the ability to stand, walk, or hold objects. Peripheral neuropathy can also affect the nerves that control automatic functions such as heartbeat, bladder control, or bowel function. Patients may experience diarrhea or constipation, incontinence, sexual impotence, and high or low blood pressure. Further, the patients' skin may become dry and pale, and patients may sweat excessively and may also develop blurred vision, dizziness or fainting spells, or stomach and intestinal problems.
Not uncommonly, the nerve damage and numbness of peripheral neuropathy can lead to injuries and infections. Because sensation is limited with neuropathy, patients may be unaware of an injury such as a burn or a cut or even mild or severe external physical insult. The untreated wound or bruise may then become infected or may result in secondary issues such as clots and their sequelae. This may be common in diabetic patients who often develop neuropathy in their feet, and then develop painless cuts that can become infected. Balance and coordination may also be also affected, and thus, falling is a concern.
Various treatment options have been identified for peripheral neuropathy with a goal of managing the underlying causal condition, such as, in the case of diabetic neuropathy, controlling blood sugars. More often, however, the goal of treatment is the management of symptoms, such as the medications intended to mitigate pain. These approaches address the symptoms of peripheral neuropathy, not the nerve damage itself. Even when the underlying cause is identified and treated, the damage to the nerves, and the resulting pain, numbness, tingling, and other symptoms, must still be treated independent of the causal condition. There is little in the literature regarding treatments that improve touch sensation. Further, while many conventional treatment options attempt to address the symptoms related to nerve damage, the actual nerve damage related to peripheral neuropathy may still progress independent of the initial cause or triggering condition. For example, treatments for acute nerve pain may progress to transient and/or chronic pain. Further, chemotherapy and other therapeutic modalities may damage either or both nerves and muscles, and that damage may result in peripheral neuropathy, which may progress independent of the continuation or termination of chemotherapy. In addition, nerve pain and/or dysfunction may cause muscle damage and/or spasms that, in turn, may further exacerbate underlying peripheral neuropathy.
Pharmacologic pain management (e.g., a common approach) may be in the form of, e.g., anticonvulsants, analgesics, opioids, anti-seizure medications, topical preparations and anti-depressants. Some agents that have been used in symptomatic management include Pregabalin (LYRICA), Gabapentic (NEURONTIN), Oxacarbazine (TRILEPTAL), Topiramate (TOPOMAX), Lamotrigine (LAMICTAL), Duloxetine (CYMBALTA), Amitriptyline (ELAVIL), Nortriptyline (PAMELOR), Venlafaxine (EFFEXOR), Oxycodone CR (OXYCONTIN), Fentanyl (DURAGESIS TRANSDERMAL SYSTEMS), Methadone (DOLOPHINE), Lidocaine patches, and/or Capsaicin (ZOSTRIX) Unfortunately, these have significant, and undesirable, side effects. Additionally, as the body adjusts to these drugs over time, their effectiveness may diminish. Dosages are typically increased to provide some continuing relief. Ultimately, however, these therapeutic protocols often become ineffective. Given the lack of success of the conventional care approaches, patients with peripheral neuropathy may ultimately either live with the pain, numbness and tingling of early stage peripheral neuropathy, the motor control issues of later stage peripheral neuropathy, or live with the considerable side effects of drug treatments whose effectiveness may dissipate over time.
In addition, hyperalgesia (e.g., an increased sensitivity to pain) may be caused by long term (e.g., greater than three months) use of some pain management drugs. Further, hyperalgesia may be caused by damage to nociceptors and/or peripheral nerves, although the mechanism has not been definitively identified. Further, use of masking agents such as opioids may actually extend or exacerbate peripheral neuropathy due to failure to engage in physical activity resulting in degenerative disorders including muscle atrophy, depression, and withdrawal from day-to-day activities. Other alternative treatments have also been identified, including acupuncture, topical application of capsaicin cream, ingestion of alpha-lipoic acid and vitamin supplements, biofeedback, physical therapy, including exercise, massage, and the application of heat. These alternative treatments have seen limited success. Other alternative treatments may include ultra-sound, “cold laser” (low-power Class III), and LED-arrays. Results with these other alternatives treatments thus far, however, have been unimpressive and brought unremarkable patient relief.